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Three's Company

The Army, women with cancer and the medical community have joined forces

By Christine Haran

The following article was printed in MAMM magazine in January 2001. Permission to re-use granted by MAMM, LLC, 349 West 12th Street, New York, NY 10014

Here's a little-known fact: Since 1992, Congress has appropriated more than $1 billion for breast cancer research to-who would have guessed it?-the Department of Defense (DoD). While this might seem counterintuitive, in the last seven years the DoD's Breast Cancer Research Program (BCRP) has evolved into one of the largest funders of cancer research in the country. The program has awarded more than 2,000 medical research grants. Some of this research has already resulted in a new method of early detection; other work is promising enough to have been picked up by the National Cancer Institute (NCI).

In addition to fostering these new ideas, the BCRP has done yeoman's work in bringing young scientists into the field of breast cancer research: A third of all BCRP grants are training awards, and the investment appears to be paying off. In the 1993/94 fiscal year alone, for example, the BCRP funded 107 grants that supported more than 250 investigators in training. More than 500 publications have resulted from the 1993/94 grants. In turn, these studies have been cited almost 11,000 times in other publications, suggesting that the work of these young scientists-from studies on the impact of gene therapy on cancer cells to the development of computer-assisted mammography-is of great value to the medical community.

As a result of these successes, the Army has swayed most of its doubters. "I was wary of the ability of the army to adapt, to adjust, to meet goals," said Herceptin developer Dennis Slamon, MD, PhD, at a DoD meeting titled Era of Hope, held last June in Atlanta. "I would have bet the farm [that success] would not have happened, but I could not have been more wrong."

"It's a funny mix of cultures," acknowledges Mary-Claire King, PhD, the University of Washington geneticist who discovered the BRCA gene mutations that put women at higher risk of breast and ovarian cancer. "I'm a Berkeley '60's person. Getting orders from the army is not how we do business." Yet Dr. King, who is also a DoD grantee, admires the program for its convergence of perspectives-and how it complements the work of the NCI.

Aiming to "fill in the research gaps" left by large research agencies and to bring quality researchers into the field, the BCRP is innovative in another way as well, having established a scientific review process in which clinicians, researchers and consumers-usually women with cancer-participate as peers.

Getting Started

Scientists and advocates were initially uneasy about handing breast cancer dollars over to the military. But the U.S. Army has a long history of biomedical research, beginning in 1777 with a military small pox immunization program ordered by Gen. George Washington. Army researchers are responsible for major health advances, including the discovery that mosquitoes transmit yellow fever, the establishment of the first school of preventive medicine and public health and the development of an antityphoid vaccine.

The DoD's women's cancer research started with an election year collaboration on Capitol Hill. In 1992, the then one-year-old National Breast Cancer Coalition (NBCC), based in Washington, DC, began lobbying Congress for $300 million for breast cancer research. Meanwhile, Sen. Tom Harkin (D-IA) and then Sen. Al D'Amato (R-NY) each introduced separate pieces of legislation to have funds transferred from the DoD to the National Institutes of Health (NIH) for breast cancer research. Since the Cold War was ending, there was sentiment in Congress that some DoD funding could be put to higher use. Both efforts failed, however, due to a lack of support.

With the NBCC's guidance, Harkin and D'Amato joined forces and introduced an amendment to the DoD Appropriations Act to transfer funds within the DoD to a peer-reviewed breast cancer research program. The Army already had a small breast cancer research program for military women, but the measure proposed raising the budget from $25 million to $210 million; it passed almost unanimously.

According to NBCC president Frances Visco, once the amendment passed, the legislators and advocates planned to bend the rules and get the funds transferred to the NIH anyhow. But when she asked then NCI director Sam Broder, MD, what he planned to do differently with the infusion of money, he told her in now legendary words, "The NCI is a battleship, and a battleship doesn't turn on a dime." In contrast, Visco and her colleagues were encouraged by the DoD's enthusiasm for the project. Gen. Richard T. Travis, then head of the U.S. Army Medical Research and Materiel Command, which was to oversee the new program, told the advocates, "We've been given a mission and our job is to achieve whatever we've been given…Ladies, we're going to win this war."

After the appropriation, the DoD created the Congressionally Directed Medical Research Programs (CDMRP) to administer the project. The DoD also commissioned from the Institute of Medicine (IOM), a branch of the non-profit National Academy of Sciences, a report assessing research needs, creating a peer review structure for choosing grantees and designing management strategies.

Retired Col. Irene Rich, DNSc, then deputy director of Nursing Research at the Walter Reed Army Institute of Research, was chosen to administer the program and subsequently became director of CDMRP, which now includes an ovarian cancer research program, among others. (See "The Sister Program," page 42) "With everything we did, it was for the first time, so there was a lot of creative energy," she says.

Peer Review: Consumer Involvement

Per the IOM report, when grants proposals are submitted to the BCRP, they are reviewed within a two-tiered system-scientific peer review and programmatic review. The first tier consists of peer review panels divided by discipline that evaluate proposals based upon their scientific merit. Each panel includes two or three consumers and 11 to 16 scientific reviewers-many of whom have worked in NCI and at major cancer institutions. (To participate, consumers must be nominated by a cancer advocacy organization, submit an application and be interviewed by telephone.) Proposals are scored and then move to the second tier, the Integration Panel (IP), which consists of a rotating group of scientists, clinicians and consumers. The IP compares grants from all different disciplines and recommends to the DoD administrators those proposals that best meet the program goals.

At both levels of review, the mix of panelists serves as a challenge and an inspiration. "When we sit on the IP-basic scientists, clinicians and behavioral scientists-the three of us speak different languages," says Lynn Matrisian, PhD, chair of the department of cancer biology at Vanderbilt University School of Medicine in Tennessee. "There are advocates from different backgrounds and the army and their contractors [who organize the review meetings]. There are all these different perspectives. The fact that we can come up with an exciting program is a real coup for teamwork."

Consumers' involvement has been well-received by the vast majority of researchers involved. CDMRP director Lt. Col. Kenneth A. Bertram, MD, PhD, like many scientists and clinicians in the program, says he admires "the passion the [advocates] bring to the table [as well as] their perspective. Science can sound so beautiful but...when the woman sitting next to you has metastatic breast cancer, it draws you into [thinking] 'what can I get out the door here and now.'"

Rosalee Luis, diagnosed with breast cancer in 1989 and bone metastases in 1992, is one of those women at the table. She says she represents an unseen population, since most women with metastatic cancer are too busy fighting the disease to serve as consumer representatives. A graduate of the NBCC advocacy training program Project Lead, Luis was nominated to apply for the peer review board by the Florida Breast Cancer Coalition. Once selected, she reviewed and critiqued 19 proposals before participating in the three-day peer review meeting.

Luis, who was mentored by a consumer who had participated in peer review the year before, says the work was well worth it, as consumer involvement is vital to the medical community. "I feel that the DoD is sending a message to the National Institutes of Health, to hospital review boards, to state review boards, that consumers have a legitimate role [in decision-making]," she says, noting that the consumer role on the IP is equal to the one played by scientists.

"This program has had an incredible impact on the way science is done and the way scientists think about advocates," agrees NBCC's Visco. "In the beginning, they looked at us with trepidation. They thought we were going to [focus] on our pet peeve or try to save our friend's life." Visco says one scientist told her, "'I've come to realize you want what we want-you want the best science.'"

There is some apprehension that consumer panelists are drawn from a relatively small group of people. "My only concern is that we need to expand our pool of consumers, so we don't have the same people doing reviews," says Otis W. Brawley, MD, director of the NCI's Office of Special Populations Research, speaking of the consumer process in the NCI and the DoD. This view is shared by a few others, including former IP member Deborah Collyar, president of the California-based PAIR: Patient Advocates In Research, who thinks that the consumer selection policy may be stifling diversity on the panel. "A wider range of breast cancer advocacy could be useful," she says, though she adds, "It's an important program for breast cancer advocates to support."

The Portfolio

Every January, the IP has a three-day vision setting meeting in which it evaluates the past year's grants as well as the current state of research at large, and determines its priorities for the upcoming year. Project Lead graduate and Greater Baltimore Washington Advocacy Group member Rosemary Rosso joined the IP last year after three years as a peer reviewer. Rosso says the meeting gives the program, which has no specific directives from Congress, great flexibility. "Every year [the IP] looks at and re-evaluates whether there are types of research that would be valuable but aren't being done anywhere else," she says. "It gives the panel the opportunity to reinvent itself every year."

The IP tries to ensure that it is funding research from a variety of disciplines, such as molecular biology, genetics and behavioral science. In addition, new types of awards can be introduced every year. This year's awards include Idea Grants, for which pilot data is not required; postdoctoral fellowships; grants that help bring bench research to the clinic; and awards specifically for Historically Black Colleges and Universities/Minority Institutions (HBCU/MI). "We think of the program as a portfolio of investments," says Anna D. Barker, PhD, president and CEO of BIO-NOVA, a biotech company in Portland, Oregon, and chair emeritus of the IP.

A considerable chunk of the BCRP's budget goes to Idea Grants, which are given to scientists who have an idea they'd like to explore, but not the early data needed to get an NCI grant. "NCI does big grants very well," Barker says. "We felt we'd like to focus on areas of need."

Susan Love, MD, an adjunct professor of surgery at the University of California Los Angeles School of Medicine and medical director of the Susan Love MD Breast Cancer Foundation, received an Idea Grant to create a medical device for conducting ductal lavage, a means of examining milk duct cells for cancer, in 1994. "At the time, there were no places I could get money," Dr. Love says, because she'd never done research and her idea was unconventional. After gathering data on ductal lavage with funds from the Idea Grant, Love received a larger three-year contract with the DoD. She went on to establish a company to develop two ductal lavage products, which are now Food and Drug Administration approved. "[My idea] was high risk, and yet it turned out to be a risk worth taking," she says. "We're going to see more evidence of this."

Getting established researchers into the field to try new ideas is another one of BCRP's primary aims. Vanderbilt's Matrisian, who has a degree in molecular biology, is an example of this concept at work. Matrisian had worked in skin and colon cancer for more than 10 years, but when the BCRP first put out the call for grant proposals, she applied for and got four grants to study matrix metalloproteinases (MMPs) in breast cancer, as well. MMPs contribute to metastasis of cancer. After gathering preliminary data using DoD funding, Matrisian received an NCI grant. Her lab is still receiving NCI funding for breast cancer. "The [BCRP] gets people like myself into the field," she says. "Breast cancer is difficult because of its hormonal influences. But the DoD program made me say, 'Yes, I want to study it.'"

Another goal of the BCRP is to reach young scientists. Brittney-Shea Herbert, PhD, of the University of Texas Southwestern Medical Center at Dallas, is one such young researcher. Herbert, whose mother had breast cancer, received a BCRP postdoctoral fellowship this year to study telomerase inhibitors. Telomerase, which appears in 90 percent of cancer cells, keeps cancer cell chromosomes from shortening, giving them immortality. The inhibitor shortens chromosomes on cancer cells so they behave like normal cells.

Herbert says that without the BCRP, she might not be doing this research. "Coming straight out of getting a PhD, it's hard to find fellowships to establish [yourself]," Herbert says. "I think I've now situated myself into having a career in breast cancer research."

In addition to attracting new and established researchers, the BCRP is trying to encourage grant proposals on special populations, and proposals by scientists who are members of ethnic minorities. In 1999, the BCRP created two new grant mechanisms to address these issues: The Historically Black Colleges and Universities/Minority Institutions Focused Training Award and the HBCU/MI Partnership Training Award. The training award is designed to put HBCU/MIs, which often lack infrastructure, in a position to submit high-quality proposals; the partnership award helps establish collaborations between HBCU/MIs and large institutions, so that the smaller institutions can have access to the large centers' experience and facilities.

Grant applications for these awards are low, and several former members of the IP are concerned that momentum on this issue may be lost. "I think [minority initiatives] are still on their plate, but I don't think it has as much push as it [once] did," says former IP member Lovell Jones, PhD, director of the Center for Research on Minority Health at MD Anderson Cancer Center in Houston.

Lt. Col. Stacey Young-McCaughan, PhD, deputy director of the BCRP, agrees that the program "has a long way to go," but adds that "we've worked hard to get resources out to minority institutions."

Era of Hope: Seeing the results

The BCRP has held two conferences at which grant recipients present their data. The exciting mix of participants at the second conference, last June, included clinicians, military personnel, scientists from a variety of disciplines and women diagnosed with cancer. The participants shared ideas on a range of topics, from the biological characteristics of premalignant cells to the impact of support groups on young women with children. "I began to see the first Era of Hope, and-it was confirmed at second-that the money that's gone into the DoD, especially the Idea Awards, is beginning to pay off," says Ngina Lythcott, DrPH, associate dean of the Joseph L. Mailman School of Public Health at Columbia University in New York City and a returning IP member. "I see the cutting edge of breast cancer research being pushed back directly because of the DoD program."

Despite the success of the BCRP, it is not yet a permanent part of the DoD. Every year, advocates must lobby for new funding, and prove the program's worth to Congress. Some feel this hinders the program. "It's hard to plan ahead, so we just have to do our best each year," Barker says. Yet Visco suggests the uncertainty may keep the program fresh. "The NBCC is committed to lobbying to continue the program so long as it's quality science and activists are a part of the progress," she says. "If it becomes a bureaucracy…we'd lobby against it being funded."

Advocates are satisfied that the BCRP is continuing to conduct quality and innovative research. Peer review panel member Luis seems to speak for many women with cancer when she says, "There needs to be more money for [this kind of] quality research because that's where the hope lies."